Genetic variation in drug metabolism, transport and toxicity will be studied in man and in animal experimental models, particularly in genetically defined strains of inbred mice, and in isolated hepatocytes and leukocytes derived from man or the inbred mouse strains. Specific emphasis is placed on investigation of 1) genetic differences in drug metabolizing microsomal (P-450) enzymes; 2) mechanism and pharmacogenetic aspects of propranolol transport in isolated cells; 3) pharmacogenetics of arylamine drugs and carcinogens; 4) pharmacogenetics of hemolytic oxidant drug sensitivity; and 5) relationship between genetic variants of human and mouse arylesterases, drug metabolism and organophosphate toxicity.